Month 2019
Design, Synthesis, and Evaluation of Tetraethylene Glycol-Tethered Isatin–1,2,3-
Triazole–Coumarin Hybrids as Novel Anticancer Agents
(1H, s, Ar─H), 7.18 (1H, d, Ar─H), 7.68 (1H, d, Ar─H),
7.73 (1H, s, Ar─H), 8.33 (1H, s, triazole─H). ESI-MS m/
z: 581 [M + H]+. Elemental Anal. Calcd (%) for
C29H29FN4O8: C, 60.00; H, 5.03; N, 9.65. Found: C,
59.76; H, 4.82; N, 9.46.
Ar─H), 7.34 (1H, t, Ar─H), 7.72 (1H, d, Ar─H), 7.82
(1H, d, Ar─H), 8.31 (1H, s, triazole─H). ESI-MS m/z:
592 [M
C30H33N5O8: C, 60.90; H, 5.62; N, 11.84. Found: C,
60.71; H, 5.39; N, 11.63.
+
H]+. Elemental Anal. Calcd (%) for
3-(Hydroxyimino)-1-(2-(2-(2-(2-(4-(((4-methyl-2-oxo-2H-
3-(Methoxyimino)-5-methyl-1-(2-(2-(2-(2-(4-(((4-methyl-2-
oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)
ethoxy)ethoxy)ethoxy)ethyl)indolin-2-one (9h). Yield: 70%.
chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)
ethoxy)ethyl)indolin-2-one (9d).
Yield: 65%. 1H-NMR
(400 MHz, DMSO-d6): δ 2.40 (3H, s, ─CH3), 3.37–3.40
(6H, m, 3 × ─CH2─), 3.46 (2H, t, ─CH2─), 3.61 (2H, t,
─CH2─), 3.73 (2H, t, ─CH2─), 3.84 (2H, t, ─CH2─),
4.46 (2H, t, ─CH2─), 5.21 (2H, s, ─CH2O─), 6.25 (1H,
s, Ar─H), 6.85 (1H, d, Ar─H), 6.98 (1H, d, Ar─H),
7.06–7.10 (2H, m, Ar─H), 7.57–7.62 (2H, m, Ar─H),
7.69 (1H, d, Ar─H), 8.32 (1H, s, triazole─H), 12.46
(1H, brs, NOH). ESI-MS m/z: 578 [M + H]+. Elemental
Anal. Calcd (%) for C29H31N5O8: C, 60.30; H, 5.41; N,
12.13. Found: C, 60.03; H, 5.17; N, 11.95.
1H-NMR (400 MHz, DMSO-d6): δ 2.25 (3H, s, ─CH3),
2.40 (3H, s, ─CH3), 3.36–3.40 (6H, m, 3 × ─CH2─),
3.45 (2H, t, ─CH2─), 3.62 (2H, t, ─CH2─), 3.73 (2H, t,
─CH2─), 3.84 (2H, t, ─CH2─), 4.19 (3H, s, NOMe),
4.44 (2H, t, ─CH2─), 5.20 (2H, s, ─CH2O─), 6.24 (1H,
s, Ar─H), 6.79 (1H, d, Ar─H), 7.01 (1H, d, Ar─H),
7.11–7.13 (2H, m, Ar─H), 7.62–7.66 (2H, m, Ar─H),
8.32 (1H, s, triazole─H). ESI-MS m/z: 606 [M + H]+.
Elemental Anal. Calcd (%) for C31H35N5O8: C, 61.48; H,
5.82; N, 11.56. Found: C, 61.24; H, 5.56; N, 11.38.
3-(Hydroxyimino)-5-methyl-1-(2-(2-(2-(2-(4-(((4-methyl-2-
oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)
ethoxy)ethoxy)ethoxy)ethyl)indolin-2-one (9e). Yield: 72%.
5-Fluoro-3-(methoxyimino)-1-(2-(2-(2-(2-(4-(((4-methyl-2-
oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)
ethoxy)ethoxy)ethoxy)ethyl)indolin-2-one (9i). Yield: 48%.
1H-NMR (400 MHz, DMSO-d6): δ 2.28 (3H, s, ─CH3),
2.41 (3H, s, ─CH3), 3.34–3.38 (6H, m, 3 × ─CH2─),
3.45 (2H, t, ─CH2─), 3.62 (2H, t, ─CH2─), 3.74 (2H, t,
─CH2─), 3.85 (2H, t, ─CH2─), 4.44 (2H, t, ─CH2─),
5.22 (2H, s, ─CH2O─), 6.26 (1H, s, Ar─H), 6.79 (1H,
d, Ar─H), 7.01 (1H, d, Ar─H), 7.15 (1H, s, Ar─H),
7.32–7.35 (2H, m, Ar─H), 7.71 (1H, d, Ar─H), 8.31
(1H, s, triazole─H), 12.38 (1H, brs, NOH). ESI-MS m/z:
1H-NMR (400 MHz, DMSO-d6): δ 2.42 (3H, s, ─CH3),
3.36–3.41 (6H, m, 3 × ─CH2─), 3.46 (2H, t, ─CH2─),
3.64 (2H, t, ─CH2─), 3.75 (2H, t, ─CH2─), 3.84 (2H,
t, ─CH2─), 4.18 (3H, s, NOMe), 4.45 (2H, t,
─CH2─), 5.22 (2H, s, ─CH2O─), 6.24 (1H, s, Ar─H),
6.81 (1H, d, Ar─H), 6.98 (1H, d, Ar─H), 7.04 (1H, s,
Ar─H), 7.16 (1H, d, Ar─H), 7.68 (1H, d, Ar─H), 7.74
(1H, s, Ar─H), 8.32 (1H, s, triazole─H). ESI-MS m/z:
592 [M
+
H]+. Elemental Anal. Calcd (%) for
610 [M
+
H]+. Elemental Anal. Calcd (%)
C30H33N5O8: C, 60.90; H, 5.62; N, 11.84. Found: C,
60.62; H, 5.36; N, 11.58.
for C30H32FN5O8: C, 59.11; H, 5.29; N, 11.49. Found:
C, 58.82; H, 5.04; N, 11.20.
5-Fluoro-3-(hydroxyimino)-1-(2-(2-(2-(2-(4-(((4-methyl-2-
oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)
ethoxy)ethoxy)ethoxy)ethyl)indolin-2-one (9f). Yield: 63%.
3-(Ethoxyimino)-1-(2-(2-(2-(2-(4-(((4-methyl-2-oxo-2H-
chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)
ethoxy)ethyl)indolin-2-one (9j). Yellow solid, yield: 55%.
1H-NMR (400 MHz, DMSO-d6): δ 2.42 (3H, s, ─CH3),
3.37–3.40 (6H, m, 3 × ─CH2─), 3.46 (2H, t, ─CH2─),
3.66 (2H, t, ─CH2─), 3.74 (2H, t, ─CH2─), 3.84 (2H, t,
─CH2─), 4.47 (2H, t, ─CH2─), 5.24 (2H, s, ─CH2O─),
6.26 (1H, s, Ar─H), 6.88 (1H, d, Ar─H), 7.03 (1H, d,
Ar─H), 7.09 (1H, s, Ar─H), 7.17 (1H, d, Ar─H), 7.67
(1H, d, Ar─H), 7.71 (1H, s, Ar─H), 8.32 (1H, s,
triazole─H), 12.32 (1H, brs, NOH). ESI-MS m/z: 596
[M + H]+. Elemental Anal. Calcd (%) for C29H30FN5O8:
C, 58.48; H, 5.08; N, 11.76. Found: C, 58.21; H, 4.83;
1H-NMR (400 MHz, DMSO-d6):
δ 1.38 (3H, t,
NOCH2CH3), 2.42 (3H, s, ─CH3), 3.35–3.39 (6H, m,
3 × ─CH2─), 3.46 (2H, t, ─CH2─), 3.64 (2H, t,
─CH2─), 3.75 (2H, t, ─CH2─), 3.84 (2H, t, ─CH2─),
4.42–4.50 (4H, m, ─CH2─ and NOCH2CH3), 5.21 (2H,
s, ─CH2O─), 6.26 (1H, s, Ar─H), 6.90 (1H, d, Ar─H),
7.03 (1H, d, Ar─H), 7.11–7.13 (2H, m, Ar─H), 7.30
(1H, t, Ar─H), 7.70 (1H, d, Ar─H), 7.81 (1H, d, Ar─H),
8.32 (1H, s, triazole─H). ESI-MS m/z: 606 [M + H]+.
Elemental Anal. Calcd (%) for C31H35N5O8: C, 61.48; H,
N, 11.52.
5.82; N, 11.56. Found: C, 61.29; H, 5.61; N, 11.32.
3-(Ethoxyimino)-5-methyl-1-(2-(2-(2-(2-(4-(((4-methyl-2-
oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)
ethoxy)ethoxy)ethoxy)ethyl)indolin-2-one (9k). Yield: 49%.
3-(Methoxyimino)-1-(2-(2-(2-(2-(4-(((4-methyl-2-oxo-2H-
chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)
ethoxy)ethyl)indolin-2-one (9g).
(400 MHz, DMSO-d6): δ 2.46 (3H, s, ─CH3), 3.36–
3.40 (6H, m, 3 × ─CH2─), 3.46 (2H, t, ─CH2─), 3.63
(2H, t, ─CH2─), 3.74 (2H, t, ─CH2─), 3.83 (2H, t,
─CH2─), 4.21 (3H, s, NOMe), 4.45 (2H, t, ─CH2─),
5.23 (2H, s, ─CH2O─), 6.26 (1H, s, Ar─H), 6.91 (1H,
d, Ar─H), 7.04 (1H, d, Ar─H), 7.10–7.13 (2H, m,
Yield: 59%. 1H-NMR
1H-NMR (400 MHz, DMSO-d6):
δ 1.36 (3H, t,
NOCH2CH3), 2.24 (3H, s, ─CH3), 2.40 (3H, s, ─CH3),
3.36–3.40 (6H, m, 3 × ─CH2─), 3.46 (2H, t, ─CH2─),
3.63 (2H, t, ─CH2─), 3.74 (2H, t, ─CH2─), 3.84 (2H, t,
─CH2─), 4.42–4.48 (4H, m, ─CH2─ and NOCH2CH3),
5.20 (2H, s, ─CH2O─), 6.25 (1H, s, Ar─H), 6.80 (1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet